Current state of study on moyamoya disease in Japan☆

Moyamoya disease may present with either hemorrhagic or ischemic strokes. Surgical bypass has previously demonstrated superiority when compared to natural history and medical treatment alone. The best bypass option (direct vs. indirect), however, remains controversial in regard to adult ischemic symptomatic moyamoya disease. Multiple studies have demonstrated clinical as well as angiographic effectiveness of direct bypass in adult hemorrhagic moyamoya disease. In particular, there are limited data regarding strategies in the setting of failed indirect bypass with recurrent hemorrhagic strokes. Here, we describe a salvage procedure.

We describe a case of a 52-year-old man who presented with hemorrhagic moyamoya disease and failed previous bilateral encephaloduroarteriosynangiosis (EDAS) procedures at an outside institution. On a 3-year follow-up diagnostic cerebral angiogram, no synangiosis was noted on the right side and only minimal synangiosis was present on the left. The left hemisphere was significant for a left parietal hypoperfusion state. We performed a salvage left proximal superficial temporal artery to distal parietal M4 middle cerebral artery bypass using the descending branch of the lateral circumflex artery as an interposition graft with preservation of the existing EDAS sites.

The patient underwent the procedure successfully and recovered well with resolution of headaches and no further strokes or hemorrhages on the 1-year follow-up magnetic resonance imaging of the brain.

This case presents the use of a salvage direct bypass technique for recurrent symptomatic hemorrhagic moyamoya disease after failed EDAS. The strategy, approach, and technical nuances of this unique case have implications for revascularization options.

Abnormal collateral channels, so-called moyamoya vessels, play a critical role to compensate cerebral ischemia, but carry the risk for hemorrhagic stroke in moyamoya disease (MMD). The present study was aimed to clarify if superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-myo-duro-arterio-pericranial synangiosis (EDMAPS) can efficiently regress the abnormal collateral channels in MMD patients.

This study included 92 hemispheres of 61 MMD patients who underwent STA-MCA anastomosis combined with EDMAPS between 2013 and 2019. There were 17 children and 44 adults. We retrospectively analyzed the findings on cerebral angiography before and 3 to 6 months after surgery, including Suzuki's angiographical stage, the development of surgical collaterals, and the extent of abnormal collateral channels such as lenticulostriate, thalamic, and choroidal channels.

Following surgery, no pediatric and adult patients experienced any stroke during follow-up periods (40.2±25.5 and 54.9±19.7 months, respectively). Suzuki's stage significantly advanced in both adult and pediatric patients after surgery (P=0.042 and P<0.001). In adult patients, all of the lenticulostriate, thalamic, and choroidal channels significantly regressed after surgery (P<0.001, P=0.012, and P=0.004, respectively). In pediatric patients, however, lenticulostriate and choroidal channels significantly regressed (P=0.005 and P=0.034, respectively). Correlation analysis revealed that the development of surgical collaterals determined the postoperative regression of choroidal channels (P<0.001).

STA-MCA anastomosis and EDMAPS may be one of the most effective procedures to widely provide surgical collaterals to the operated hemispheres and prevent not only ischemic but also hemorrhagic stroke by regressing the hemorrhage-prone abnormal collateral channels in MMD.

Moyamoya disease is an unusual form of chronic cerebrovascular occlusive disease that is characterized by angiographic findings of bilateral stenosis or occlusion at the terminal portion of the internal carotid artery together with an abnormal vascular network at the base of the brain. Clinical symptoms and signs are the manifestations of cerebrovascular events secondary to the intracranial vascular lesions, including hemorrhagic stroke, ischemic stroke, transient ischemic attacks (TIAs) and seizure. Ischemic events are common in childhood, whereas hemorrhagic strokes are frequently seen in adulthood. Incidence is high in Japan and in east Asia. The female-to-male ratio is 1.8:1. Although genetic linkage analysis demonstrated that hereditary factors may be involved in susceptibility to moyamoya disease, etiology has not been fully elucidated yet. Ischemic and hemorrhagic lesions and major arteries are evaluated by CT, MRI, angiography, MR angiography (MRA), and carotid ultrasonography. Antiplatelet agents are prescribed to prevent recurrent ischemic attacks, although they have never been tested thoroughly in clinical trials. Surgical revascularization including direct bypass surgery, indirect bypass surgery, and a combination of the two has been performed to give additional collateral flow to the ischemic brain. A recent multicenter randomized controlled study supported preventative effect of direct bypass against rebleeding in adult-onset hemorrhagic moyamoya disease.

Fabry disease is an X-linked recessive disorder caused by reduced alpha-galactosidase activity for which enzyme replacement therapy is available. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a small-vessel stroke disorder caused by mutations in the NOTCH3 gene. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy is a stroke disorder caused by mutations in the HTRA1 gene. Homocysteinemia, commonly due to cystathionine-beta-synthase deficiency, can be treated with restriction in dietary methionine and vitamin B6 supplementation. Mitochondrial mutations can lead to a syndrome of encephalopathy, lactic acidosis, and stroke-like episodes known as mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes. In children with sickle cell disease, transcranial Doppler ultrasound can define populations at high risk of stroke and transfusion therapy can dramatically reduce the risk of stroke. Mutations in COL4A1 can cause small-vessel stroke, cerebral hemorrhage, and the hereditary angiopathy, nephropathy, aneurysms, and cramps syndrome. Several single-gene disorders cause cerebral amyloid angiopathy. Several single-gene disorders cause cerebral cavernous malformations. Genome-wide association studies have identified risk loci for large-vessel and cardioembolic stroke.

There has been an increasing prevalence of Moyamoya disorder (MMD) reported from recent US literature. There is a paucity of data available regarding trends of prevalence and epidemiological factors in the United States. To goal of this study was to test the hypotheses that racial-, sex-specific MMD hospitalizations and epidemiological factors have been increasing in the United States over the last decade.

In this retrospective observational study, using the National Inpatient Sample (NIS) database from 2005 to 2016, MMD-related hospitalizations in patients aged ≥18 years were identified. Trends of epidemiological factors were analyzed over time using the linear regression model with the significance of differences in trend over time assessed using the Wald test. Sex- and race-specific burden of MMD were calculated using the annual US Census data. Joinpoint regression model was used to evaluate trends of hospitalizations over time.

A total of 24,484 adult hospitalizations were identified from January 2005 to September 2015 after excluding <18 years. Among them, approximately ~90% were aged ≤60 years, and 73.5% were females. The most common vascular and non-vascular presentations were ischemic stroke (17.3%) and seizures (21%), respectively. The trend of antithrombotic therapy has increased, while extracranial-intracranial bypass has remained stagnant. The actual average hospitalizations of MMD was 10.4 cases/ million population/year (range 4.1–17.9) and varied significantly by sex (females 14.7 [range 6.2–23.6] and males 5.9 [range 1.8–11.9]) over the 2005 to 2016 study period. The burden of hospitalizations also differed by race (African Americans 40.6 [range 32.8–63.7], Asians 24.8 [15.4–34.8], Non-Hispanic Whites 8.1 [range 6.4–11.5], and Hispanics 8.4 [2.8–12.8]) over the 2010 to 2016 study period. Joinpoint regression analysis showed an increasing overall MMD trend across the study period (+11.7%; P < 0.001), which was higher in males (+14.5% vs. +10.7%; P < 0.001). The Hispanic group had significantly increased hospitalizations over the years (+20.2%; P < 0.001).

Although overall more prevalent in females, MMD-related hospitalizations are increasing more rapidly in males. Among the racial subpopulations, African Americans had the highest MMD-related hospitalizations, even higher than Asian Americans. MMD-related hospitalizations have increased quicker in Hispanics than in any other racial group.

Variable Moyamoya disease (MMD) genotypes and phenotypes between different races have been suggested previously. This study investigates differences in surgical complications and response to revascularization among Asian patients with MMD compared with other ethnicities in North America.

From a database of 185 patients with moyamoya presenting to our institution between 1994 and 2015, 85 patients with MMD underwent surgery and constituted the study cohort. Baseline characteristics before surgery, procedure-related complications, length of hospital stay, and outcome variables including stroke and functional outcome were compared between Asian and non-Asian patients. Kaplan−Meier survival analyses were used to compare time to ipsilateral stroke and any cerebrovascular event after bypass.

Our surgical cohort consisted of 27% (23/85) Asian and 73% (62/85) non-Asian patients with MMD with a bimodal age distribution. Among the subset of patients who presented with stroke (n = 55), hemorrhage was significantly more common among Asian patients (P = 0.007). In 120 revascularization procedures, per-operative complication rates were greater among Asian patients while controlling for age, type of surgery, and stroke history (odds ratio 2.94; 95% confidence interval 1.16–7.48; P = 0.02). The mean follow-up time after surgery was 4.57 years. Ipsilateral cerebrovascular event rates were 4.77 per 100 person-years in non-Asian patients and 6.51 per 100 person-years in Asians (P = 0.66). Unfavorable modified Rankin Scale scores (>2) were found in 22% of Asian patients and 8% of non-Asian patients on last follow-up (P = 0.13).

Asian patients with MMD may be more susceptible to surgical complications and may differ from other races in their response to revascularization. Further long-term prospective studies are needed to investigate these findings.